Myocarditis is an important cause of heart failure among adolescents and young adults. While about 33 percent of myocarditis patients recover, the remainder may develop chronic dilated cardiomyopathy which accounts for 25 percent of all heart failures in North America. Coxsackievirus B3 (CB3) infections have been implicated in about 40 percent of myocarditis cases. Antiviral drugs and immunosuppressive therapies have given mixed results, requiring further research in order to develop effective therapies. Studies of Coxsackievirus-induced myocarditis in mice have provided valuable information about the role of the adaptive, acquired immune response to CB3 in the development of autoimmune myocarditis. Recently, there has been renewed interest in how the innate immune response to infection may affect the development of adaptive immunity. However, very little research has been conducted on how the early, innate immune response to Coxsackievirus infection effects the development of autoimmune myocarditis. The aim of this proposal is to delineate the role of "early" cytokines and immune cells involved in innate immunity in the development of acute and chronic CB3-induced myocarditis. We hypothesize that the initial innate immune response to CB3 determines whether the adaptive immune response leads to the later development of autoimmune myocarditis.